STUDIES ON MACROCYCLIC ACETYLENIC COMPOUNDS THESIS presented to the University of Glasgow for the Degree of Ph.D. by DENIS' McMASTER 1970 ProQuest Number: 11011953 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11011953 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 SUMMARY 4 Section I j In an attempt to synthesise compounds related to the asa| yet unknown 1,6-didehydro-[10]-annulene, intermolecular Castrol type coupling of the cuprous salts of l-(o-iodophenyl)-2-pro- 1 pyn-l-ol and derivatives was investigated. Intermolecular coupling of derivatives suggested by model reactions was either unsuccessful, however, or gave a complex mixture, the nature of which could not be clarified. The synthesis of 'half-cyclised’ compounds, formally only one stage away from the desired ten membered ring system was achieved, however, and some new examples of the Castro reaction, including some anomalies and failures, were discovered. Section II Intermolecular Castro-type coupling of the cuprous salt of m~iodophe;iylacetylene was found to give a complex mixture, the major component of which was shown to be the ’cyclic pentamer1 derived from five molecules of the cuprous salt. Evidence was obtained for the presence of similar cyclic compounds of lower and higher molecular weight. A series of compounds resulting from mixed oxidative and Castro-type coupling was also isolated from the reaction product. ACKNOWLEDGEMENTS I express my thanks to Professor R.A. Raphael for his close interest and guidance throughout the course of the work described in this thesis and to G-eigy (U. K.) Limited for providing a maintenance award. My thanks are also due to Mr. J.M.L. Cameron and his staff for micro-analytical services, to Mrs. P. Lawrie and Mrs. A.M. McNiven for infrared spectra, to Mr. J. G-all, Mrs. S.J. Hamilton and Mrs. M. M. Kirkland for nuclear magnetic resonance spectra, to Mr. A. Ritchie for mass spectra, and to Mr. G-. Milmine and his staff for technical assistance. S E C T I O N I .INTRODUCTION In 1865, Kekule suggested that benzene, which had been known for some time to be closely related to the naturally occurring, carbon rich 'aromatic* compounds, 1 was best described by the cyclohexatriene structure, p He later modified this to a 'dynamic' structure, involving continuous interchange between two 'Kekule* forms, and this picture of a symmetrical benzene molecule became ■3 generally accepted. An interpretation of the special stability of benzene in electronic terms was first given in 1925 by Armit and Robinson,^ with the idea of an ^aromatic sextet' of electrons . The real basis, however, for much of the recent interest in aromatic compounds, and in particular, higher homologues of benzene, lies in the suggestion of Huckel, 5 on the basis of molecular orbital theory, that fully conjugated monocyclic polyolefins should be aromatic, if they contain (4n + 2) tt electrons and are planar. Perhaps surprisingly, this postulate did not arouse any immediate r interest on the part of organic chemists until Dewar, in 1945, suggested that both stipitatic acid and colchicine contained a seven membered aromatic ring related to the cycloheptatrienyl (tropylium) cation, which contains six t t -electrons and had been predicted by Huckel to be a stable system. Considerable speculation on the syn­ thesis and possible properties of higher homologues of benzene occurred in the following ten to fifteen years, and after the tropylium cation had been synthesised in 8 1954 by Doering and Knox, the first homologue of benzene comprising a monocyclic fully conjugated polyene (or annulene) containing (4n + 2) tt electrons, [ 18]-annulene (l), was synthesised in 1959 by Sondheimer and V/olovskyB^ Since then, great interest has been shown in both the synthesis and theoretical aspects, not only of the annulenes themselves, but of various related compounds. For example, many *dehydroannulenesf have been synthesised by Sondheimer and his group, in which double bonds have been replaced by triple bonds or eumulene type systems, and in which Huckel?s rule can be applied to the 'out of plane1 tt electrons. In addition, in some polycyclic systems, the peripheral electrons can be considered as a monocyclic system, with the cross-links as only minor perturbations, and several systems of this type have been synthesised. Evidence from all these types of compound supports the validity of the Huckel (4n + 2) rule, up to at least 18 tt electron systems. Several recent reviews^ and a monograph"^ have appeared, summarising the present state of knowledge. If we consider the annulenes, however, it can immediately be seen that certain factors arise which are not present in the case of benzene. In the smallest member after benzene of the (4n + 2) series, [10]- annulene, the possible planar configurations required by Huckel for aromaticity involve serious interaction of - 4 - two internal hydrogens (2), considerable angle strain (3), or in a third form (4), a combination of both types of strain. Similar, though not so congested, hydrogen interactions occur in higher members of the series, and for this reason Mislow,^a in 1952, considered that [30]- annulene (5) would be the first member which could attain 7b planarity. Baker considered Mislow’s view •unduly pessimistic, on the grounds that complete planarity is not always necessary even in benzenoid aromatic compounds, and suggested that the smallest cyclopolyene which would exhibit aromatic properties would probably be [18]- annulene (l). Theoretical objections also exist to the 12 simple.Huckel rule. Longuet-Higgins and Salem have stated that above a certain, undefined ring size, bond alternation will occur and any special properties will be lost. Recent calculations by Dewar and Gleicher13 suggest that this may occur between [22]- and [26]- annulene. Another difficulty occurs when we consider how any special ’aromatic* properties might he observed. The word ’aromatic’, as applied to chemical compounds, has always been rather loosely defined.1^ Thus there has always been a conflict between whether ’aromatic’ should describe compounds with benzene like structure, or benzene like properties, such as relative stability and IS tendency to undergo substitution reactions. Typical benzenoid properties, however, such as the tendency to undergo substitution reactions, are far from satisfactory as a criterion of arornaticity. These properties are connected with the excited state of the molecule and are known to vary widely in compounds such as furan, benzene and resorcinol, for example, which are all generally accepted as aromatic. On the basis of chemical behaviou indeed, [14]- and [l8]-annulene appeared to behave very much like polyenes and indeed resembled the 4n annulenes in reactivity."^ - 6 A raore useful concept In discussing aroraaticity is tt electron delocalisation. For this to be effective, the molecule must be approximately planar, and it results in the equivalence, or near equivalence, of all the carbon-carbon bonds. Belocalisation of the tt electrons also has a marked effect on the nuclear magnetic resonance spectrum, in that in an aromatic molecule, an induced dia­ magnetic ring current is set up in an applied magnetic field, with the result that protons on the outside of the ring are deshielded, or move to lower field values, whereas those inside the ring are shielded and move to IV 18 higher field values, Elvidge and Jackman havein fact defined an aromatic compound as one which will sustain an induced (diamagnetic) ring current. In some cases (e.g. [14] -annulene^c > , because of the rapid interchange of the inner and outer protons, the nuclear magnetic resonance spectrum must be observed at low temperature for this effect to be noticed. It was originally thought that the 4n annulenes would be olefiriic in character, rather like cyclooctatetraene, and that the nuclear magnetic resonance spectra would show only olefinic absorption. This appeared to be the 20 case until in 1966, work was published on the low temperature nuclear magnetic resonance spectra of [l6]- 21 annulene by Schroder and 0th, and of [24]-annul.ene by 22 Calder and Sondheimer, which showed that these com­ pounds exhibit an *anti-aromatic' spectrum, in which the lower protons absorb at low field and the outer protons at high field. This has been attributed to the exist­ ence of paramagnetic ring currents in the molecule and discussions of their theoretical basis have appeared by p*z p/ longuet-Higgins, Pople and Untch, and Baer, Kuhn and 26 Regel. The existence of this effect was suggested to Pople and Untch2^ by the very high shielding (t = 5*58) 26 of the protons in 1,5,9-tridehydro-[12]-annulene (6), and similar, though not very large effects had in fact been - 8 ~ noticed earlier, though rot explained in these terms, for example in the tetradehydro-[24]-annulene (7) 27 synthesised by Sondheimer and VTolovsky in 1962. In this molecule the inner protons appear at t = 1*60 and the outer protons in a complex band at t = 4*40 - 5*02. It should be noted that although the idea of diamagnetic and paramagnetic ring currents is generally accepted, p Q their existence has been vigorously denied by Musher* At the moment, however, his views would appear to be very much in the minority.